The present invention relates generally to a medication and an implantable device, and in particular, to a medication, method and device for cardiac treatment.
Supraventricular arrhythmias such as atrial tachycardia, atrial flutter, and atrial fibrillation are characterized by rapid and frequently ineffective contraction of the atria which lead to inefficient heart performance. Atrial flutter is characterized by a rapid and regular rhythm of the atria (typically 300 flutter or f-waves/minute) but not the ventricles (typically 150 beats/minute). Atrial fibrillation is characterized by an irregular and usually rapid heart rhythm in which the atria fibrillate more than 300-350 impulses or f-waves per minute while the ventricular rate is in the range of 120-200 beats per minute. During atrial fibrillation, the electrical signals start irregularly and usually from several places in the atria and travel erratically throughout the atria, leading to blood pools and clots which increase the risk of stroke. Approximately 15-25% of all strokes can be attributed to atrial fibrillation. In addition, the cardiac output in atrial fibrillation is only 70-80 percent of normal, leading to shortness of breath and fatigue. In many cases, atrial fibrillation is associated with arterial hypertension as well as structural diseases of the heart or the lung. If untreated, the short paroxysms of atrial fibrillation can transform to persistent or permanent appearance, leading to significant complications such as stroke, cardiomyopathy and heart failure.
To restore normal heart rhythm various antiarrhythmic drugs can be used. These include quinidine, procainamide, disopyramide, flecainide, propafenone, dofetilide, ibutilide, azimilide, amiodarone and β-blockers (especially sotalol). However, such medications are only effective in 30-60% of the cases and usually lose their effectiveness over short period of time. In addition, some drugs have potentially serious side effects. Control of the heart rate can be achieved using β-blockers, calcium channel blockers and digoxin. To reduce the risks of clot formation, anticoagulant and/or antiplatelet drugs such as coumadin (warfarin) and/or aspirin are prescribed. Coumadin reduces the risk of stroke by 60-80% in people with atrial fibrillation.
In cases such drugs are not efficient in restoring sinus rhythm, one of the following procedures may be applied:
I. Electrical cardioversion: To synchronize the heart and restore a normal rhythm, an electrical shock is delivered to the patient's chest wall (sometime intracardially or transesophageal) after administration of a short-acting anesthesia.
II. Catheter ablation: Ablation of the AV node or the right and/or left atrium is performed using soft wires (catheters) which are inserted through the veins (e.g., in the groin) and guided to the heart. In AV ablation, the radiofrequency (RF) energy is delivered through the catheter to destroy the AV node. Because the ablation causes heart block, a permanent pacemaker is further implanted to maintain adequate heart rates. In atrium ablation, the catheters are used to “map” the atrium and to deliver RF energy to ablate or isolate foci that fire or propagate abnormal electrical impulses (e.g., isolation of pulmonary veins in the left atrium, or such ablation procedures as “maze” or “corridor”). The RF energy (as well other sources of energy such as freezing or cryo) produces a scar that blocks any abnormal impulses from propagating within the left, right or both atria, thus preventing atrial fibrillation from occurring.
III Implantable Device Therapy:
a. An implantable cardioverter-defibrillator (ICD) is a device designed to provide automatic conversion of ventricular fibrillation to normal rhythm by electrical shock. Some commercially available ICDs have the capacity to provide atrial electrical shock in addition to the standard ventricular therapy. Wellens et al., describe an implantable atrioverter for the treatment of atrial fibrillation (Wellens H J J, et al., 1998, Circulation, 98: 1651-6). Significant discomfort and often intolerable pain is associated with intracardiac shock therapy by implantable atrioverter resulting in the need for sedation of some patients and refusal to accept the therapy by other. Currently stand alone atrial cardioverter-defibrillators are not available.
b. A permanent pacemaker is a device that sends low energy electrical impulses to the heart muscle to maintain a suitable heart rate. The pacemaker includes a pulse generator (which contains a battery and electronic circuitry) and pacing lead(s) (wires) that deliver the impulses from the pulse generator to the right atrium, right ventricle and, in some cases, the left ventricle through the coronary sinus, and sense the spontaneous heart's electrical activity in atrium and ventricle(s). Although atrium-based pacing is associated with a lower risk of atrial fibrillation and stroke than ventricle-based pacing for patients requiring pacemakers for bradyarrhythmias, the use of pacing as a primary therapy for prevention of recurrent atrial fibrillation as well as for it treatment has not been validated.
c. Implantable devices for drug delivery are designed to monitor and control the release of a drug from the device. These devices are often used for long-term infusion of drugs in patients having chronic diseases such as diabetes mellitus, cancer, spasticity, pain and others. Usually, such pumps comprise a pressurized drug source which can be refilled while the device is implanted. Examples of implantable drug devices are described in U.S. Pat. Nos. 4,978,338, 6,541,021 and 6,689,373, 6,835,194, 6,728,574, 6,716,208, 6,572,605, 5,911,704, 5,704,910, 6,668,190, 6,444,217 and 6,342,250, all of which are fully incorporated herein by reference.
U.S. Pat. No. 6,497,699 to Ludvig et al., entitled “Hybrid neuroprosthesis for the treatment of brain disorders”, describes a miniature apparatus for the treatment of brain disorder. The disclosed hybrid system is a combination of electronic and pharmacological devices placed and powered entirely within the human body.
U.S. Pat. No. 6,453,195 to Thompson, describes an externally mounted transdermal drug delivery device, in communication with at least one implantable medical device, designated to deliver pain analgesics prior to shock therapy by an atrial defibrillator. The drug delivery device includes an attachable strip with storage for medications and is epidermally mounted. The medications are released into the bloodstream in response to an indication that the implantable device is about to deliver a shock. The drug delivery device is adapted for use with various drugs. Further, the delivery of drugs could be controlled by the patient to provide a semi-automatic use.
U.S. Pat. No. 5,527,344 to Arzbaecher et al., discloses an implantable apparatus for automatically delivering a defibrillating drug to a patient upon the detection of the onset of atrial fibrillation. In this system, the delivery time is continuously computed and the delivery signal is emitted as function of the monitored level of atrial activity. However, the efficiency of such a device in treating atrial fibrillation was not proven, mainly due to the fact that at present no suitable defibrillating drug for conversion atrial fibrillation to sinus rhythm can be administered via such a device.
IV. Heart surgery: Patients with highly symptomatic paroxysmal, persistent and permanent atrial fibrillation not alleviated by medication or catheter ablation procedures, or have other conditions requiring heart surgery, are candidates for surgical treatment of atrial fibrillation (e.g., “maze” or “corridor” procedures). Surgical operations for atrial fibrillation have been successfully combined with operative correction of a variety of structural cardiac conditions such as valvular, ischemic, or congenital heart disease, although this entails additional risk. The mortality rate of an isolated “maze” operation is about 1%, but mortality is higher when the procedure is combined with other types of operative repair. The morbidity associated with the operation includes consequences common to thoracotomy and cardiopulmonary bypass, as well as a risk of transient or permanent reduction in left and right atrium transport function, and early postoperative atrial tachyarrhythmias. In addition, sinus node dysfunction might require a permanent pacemaker implantation. Currently, surgical operations of cardiac lesions frequently combined with intra-operative catheter ablation of atrial fibrillation.
There is thus a widely recognized need for, and it would be highly advantageous to have, a method, a drug and a device for treating atrial fibrillation devoid of the above limitations.